Effects of Base π-Stacking on Damage to DNA by Low-Energy Electrons

Abstract

In this work, we extend our earlier studies on single-strand break (SSB) formation in DNA to include the effects of base π-stacking. In thsese studies, we consider SSBs induced by low-energy electrons that attach to DNA bases' π* orbitals. Here, we conclude that the inclusion of π-stacking effects causes an increase of the energy barriers (corresponding to accessing the stretched C−O bond that break in the SSB formation) that govern the rates of SSB formation. As a result, the rates of SSB formation are predicted (in the CCC codon considered here) to lie below 0.8 × 105 s-1 for electrons having kinetic energies E ≤ 2.0 eV and thus to be not very competitive with electron autodetachment whose rate is ca. 1014 s-1. However, in the presence of even modest solvation, autodetachment is rendered inoperative, so SSBs can occur with considerable yield via the electron-attament pathway. In addition to these studies of sugar−phosphate C−O bond cleavage, we find that the barrier height for sugar−cytosine N−C bond breaking is 43 kcal/mol, which is much higher than the corresponding value estimated for the sugar−phosphate C−O bond breaking, which makes the N−C route not likely to be operative in such electron-induced SSBs.